TRAIL‐mediated apoptosis requires NF‐kB inhibition and the mitochondrial permeability transition in human hepatoma cells

Young‐Soo Kim, Robert F. Schwabe, Ting Qian, John J. Lemasters, David A. Brenner – 7 March 2007 – Tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) induces apoptosis in a wide range of malignant cells. However, several cancers, including human hepatoma, are resistant to TRAIL. In this study, we analyzed TRAIL‐induced pro‐ and antiapoptotic signaling pathways in human hepatoma cells. Nuclear factor k B (NF‐kB) was found to be a critical TRAIL‐induced antiapoptotic factor in the PLC/PRF/5, HepG2, and Hep3B cell lines.

Endothelin‐1 and heme oxygenase‐1 as modulators of sinusoidal tone in the stress‐exposed rat liver

Hauke Rensing, Inge Bauer, Jian X. Zhang, Markus Paxian, Benedikt H. J. Pannen, Yukihiro Yokoyama, Mark G. Clemens, Michael Bauer – 7 March 2007 – Heme oxygenase (HO)‐1 is up‐regulated after ischemia/reperfusion and contributes to maintenance of hepatic perfusion and integrity. Blockade of HO‐1 leads to an increased portal pressor response in the stress‐exposed liver. We tested whether the increase in portal pressure reflects unmasking of a concomitant up‐regulation of the vasoconstrictor endothelin (ET)‐1.

Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease

Feng Hong, Svetlana Radaeva, Hong‐Na Pan, Zhigang Tian, Richard Veech, Bin Gao – 7 March 2007 – Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology indluding ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time. We therefore examined the effects of 10 days of interleukin 6 (IL‐6) injection in 3 murine models of fatty liver: leptin deficient ob/ob mice, ethanol‐fed mice, and mice fed a high‐fat diet.

Serum bilirubin levels in the U.S. Population: Gender effect and inverse correlation with colorectal cancer

Stephen D. Zucker, Paul S. Horn, Kenneth E. Sherman – 7 March 2007 – Bilirubin, the primary end product of heme catabolism, is a key marker of liver and hematological disorders, and important cytoprotective properties have been ascribed to this bile pigment. The Third National Health and Nutrition Examination Survey, a comprehensive assessment of health and nutrition in the United States, was analyzed to determine the demographics and correlates of serum bilirubin levels in the general population.

New mechanism of selective killing of activated hepatic stellate cells

Milan Dodig, Kevin D. Mullen – 7 March 2007 – Background & Aims: Hepatic stellate cells play an important role in liver fibrogenesis, and hepatic stellate cell death may be involved in the termination of this response. Methods: Molecular mechanisms of hepatic stellate cell killing were studied in hepatic stellate cell/Kupffer cell cocultures. Results: Lipopolysaccharide stimulation of hepatic stellate cell/Kupffer cell cocultures, but not of hepatic stellate cell monocultures, induced profound alterations of hepatic stellate cell morphology and hepatic stellate cell death.

Sex is a major determinant of CYP3A4 expression in human liver

Renzo Wolbold, Kathrin Klein, Oliver Burk, Andreas K. Nüssler, Peter Neuhaus, Michel Eichelbaum, Matthias Schwab, Ulrich M. Zanger – 7 March 2007 – Many drugs that are substrates of CYP3A4, the major human drug‐metabolizing cytochrome P450 (CYP), show higher clearance in women than in men. Although this effect is believed to be related to drug metabolism, the underlying cause has not been elucidated.

Effects of cell proliferation on the uptake of transferrin‐bound iron by human hepatoma cells

Adrian W. M. Lee, Phillip S. Oates, Deborah Trinder – 7 March 2007 – The effects of cellular proliferation on the uptake of transferrin‐bound iron (Tf‐Fe) and expression of transferrin receptor‐1 (TfR1) and transferrin receptor‐2 (TfR2) were investigated using a human hepatoma (HuH7) cell line stably transfected with TfR1 antisense RNA expression vector to suppress TfR1 expression.

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